John Spinelli

Professor

Relevant Degree Programs

 
 

Graduate Student Supervision

Doctoral Student Supervision (Jan 2008 - Nov 2019)
Investigations into breast cancer screening participation and retention in British Columbia, Canada (2019)

Breast cancer screening programs operate across Canada and aim to reduce breast cancer mortality through early detection of breast tumours. In British Columbia (BC), a significant fraction of eligible women are not receiving regular mammograms. Research from other jurisdictions suggests that some immigrant populations participate less in screening than non-immigrants. Other research suggests that the primary care system may influence screening participation among women. Measures of primary care access, coordination and continuity in BC show recent declines, and only a small percentage of physicians are accepting responsibility for patients’ ongoing primary care needs.This thesis includes a series of population-based studies, using administrative health and other databases, to assess differences between immigrant and non-immigrant women, and among immigrant groups for: 1) breast cancer screening participation and retention; 2) breast cancer risk; and 3) differences in breast cancer stage at diagnosis. An additional study examines whether primary care factors, such as physician characteristics, or measures of physician and patient relationships, associate with screening utilization.Breast screening participation varied markedly according to country of birth, with some immigrant groups demonstrating very low participation. Among recent immigrants, the number of primary care physician visits was consistently identified as an important predictor of participation. Both stage-specific and age-specific incidence rates, showed substantial variation by country of birth. Eastern European/Central Asian and Indian immigrants demonstrated a worse stage at diagnosis compared to non-immigrants. Several primary care factors, such as low continuity of care, few physician visits, having a male physician and short duration of affiliation with a provider were associated with lower participation. The effects of these factors were stronger within some subgroups, such as low-income and some immigrant groups. Although physician factors did not show a strong relationship with retention overall, among first-time screeners, low continuity and few physician visits were associated with lower retention. These results suggest a number of areas for potential screening promotions, interventions and future research.

View record

Mammographic density and associations with breast cancer risk and genetic variation in postmenopausal women : a causal inference approach (2019)

The association between mammographic density and breast cancer risk is well known, however, the role of absolute non-dense area remains unclear. Furthermore, even though the associations between breast cancer and known risk factors differ by tumor characteristics, this has not been clearly demonstrated for mammographic density. In addition, not much is known about how the variation in breast cancer related single nucleotide polymorphisms (SNPs) is associated with mammographic density, but given its high heritability, it is possible common genetic determinants could affect both mammographic density and breast cancer. The objectives of this work were to (1) determine the association between non-dense area and breast cancer, as well as confirming the association between dense area and breast cancer, (2) assess the discriminating power captured by the non-dense area parameter on models forecasting breast cancer, (3) estimate breast cancer risk for mammographic density parameters by breast cancer tumor characteristics, and (4) evaluate the relationship between polygenic risk scores (PRS) generated developed to predict genetic risk of breast cancer with mammographic density parameters.A population-based case-control study conducted in Vancouver, BC, was used. Detailed questionnaire and clinical information, as well as measured breast density from screening mammography films, were collected. In Chapter 2 estimates of the effects of mammographic density parameters on the risk of breast cancer are computed, using causal inference methods for observational studies. Chapter 3 details the assessment heterogeneity in the relationships between mammographic density parameters and breast cancer risk, according to tumor characteristics. Chapter 4 describes the evaluations of the associations between loci linked in genome-wide association studies to breast cancer risk, and mammographic density parameters, by using recently developed PRS.Non-dense area was found to be an independent risk factor, inversely related to breast cancer risk; however it did not improve prediction over the information given by dense area or percent dense area alone. Mammographic density parameters were not associated to breast cancer tumor characteristics. Finally, limited evidence of shared genetic factors between breast cancer risk and mammographic density was observed. These findings provide important information about the association between mammographic density and breast cancer risk.

View record

Retrospective pesticide exposure assessment for studying multiple myeloma risk for farm work in British Columbia, Canada (2019)

Multiple myeloma (MM) is one of the cancer types that research has shown to be in excess among farm workers. Pesticides have been highly suspected as a risk factor, and much of the research aimed at understanding MM etiology in farm workers has focused on pesticides. However, certain methodological challenges related to the retrospective assessment of pesticide exposure have contributed to weak and at times, inconsistent, epidemiologic evidence. The aims of this research were to collect and understand the usefulness of exposure data from the literature for future exposure assessment, to develop a method for estimating cumulative pesticide exposure levels in farm workers when combined with self-reported information, and to apply this method to evaluate the relationship between pesticide exposure and MM risk among a sample of farm workers in British Columbia (BC), Canada. The first study used a systematic approach to collect and evaluate the literature to identify studies that provided quantitative dermal pesticide exposure information on farm workers. The data were extracted and evaluated for usefulness for exposure assessment development. The second study involved the development of a pesticide exposure algorithm, and its application to farm data previously collected as part of an MM case-control study conducted in BC. The results of this algorithm were compared to the results of two other methods, one of which was a previously developed and evaluated algorithm from a well-known prospective cohort of pesticide applicators. The third study was an epidemiologic analysis to evaluate the relationship between pesticide exposure and MM among farm workers identified in the BC case-control study. Pesticide exposure was assessed using dichotomous, simple metrics of exposure as well as the two algorithms from the second study to estimate cumulative pesticide exposure.Overall, the research from this dissertation contributed new knowledge and provided additional evidence to support existing knowledge on the methodological issues surrounding the study of pesticide exposure in relation to MM among farm workers. Additionally, it provided a new pesticide exposure algorithm that can be further evaluated and improved upon regarding its ability to accurately assess exposure among farm workers using self-reported historical exposure information.

View record

Occupational exposure to polycyclic aromatic hydrocarbons, breast cancer risk, and interactions with genetic variants (2017)

Polycyclic aromatic hydrocarbons (PAHs) are created by the incomplete combustion of fossil fuels, and are established human carcinogens. However, the effect of occupational PAH exposure on breast cancer is not well established. In addition, it is not known if genes involved in metabolizing xenobiotic compounds modify the risk of breast cancer in women exposed to PAHs. The objectives of this study were to (1) estimate the association between PAH exposure and breast cancer, (2) examine how variants of select xenobiotic metabolizing genes influence breast cancer risk, and (3) assess how these variants – several of which are involved in PAH metabolism – interact with PAH exposure to modify breast cancer risk. The relationships between PAH exposure, genetic susceptibility, and breast cancer were examined in a population-based case control study conducted in Vancouver, BC and Kingston, Ontario. A detailed questionnaire, including occupational history, and biological sample were collected from participants. Chapter 2 details how I developed a statistical model that predicts the probability of exceeding the permissible exposure limit for PAH through industry and occupation using workplace compliance testing data collected in the United States. Chapter 3 describes the use of the model to develop a job exposure matrix and estimate the association between PAH exposure and breast cancer. In Chapter 4, I assessed the associations between select gene variants and breast cancer, and evaluated whether there is evidence that those variants modify PAH exposure effect on breast cancer risk. Long term exposure to PAHs was identified as a risk factor for breast cancer, and risk was highest among premenopausal women and women with a first degree family history of breast cancer. Six variants in xenobiotic metabolizing genes were observed to be related to breast cancer risk, three of which are directly involved in PAH metabolism. In addition, there is evidence to support the notion that three of these variants modify the effect of PAH exposure, implicating the role gene-environment interactions have on modifying breast cancer risk. Evidence from this research points to the potential importance of monitoring and limiting occupational exposures to PAHs in order to reduce breast cancer risk in women.

View record

Late effects among young adult cancer survivors (2014)

Background and objective: Long term young adult cancer survivors (YACS) can face serious life-threatening complications in multiple organ systems, and these may become more clinically significant with aging. However, there have been limited attempts to understand the risk of late-effects in this group. Therefore, this thesis aimed: to measure the overall and cause-specific risks of late effects among YACS, including late mortality, SMN and late morbidity leading to hospitalization; to identify the characteristics influence these risks; and to examine YACS’ willingness in participating late effects studies in the future. Methods: The first three studies used data collected from Childhood Adolescent and Young Adult Cancer Survivor (CAYACS) research program, an ongoing retrospective cohort study. In the fourth study, YACS were surveyed regarding their willingness to participate in late effects studies in the future. Cox proportional hazard regression and multivariate logistic regression models were used to examine the relationship between outcomes (late effects and willingness of participation) and key socio-demographic, clinical-related factors, including the primary cancer diagnosis. Results: YACS showed increased risks of mortality, SMN and late morbidity leading to hospitalization compared with the general population. The diagnosis of the primary cancer had a significant impact on survivors’ mortality and SMN. The highest risk of mortality was observed among central nervous system (CNS) tumor survivors, whereas the highest risk of SMN were seen in survivors of lymphoma. The risk of late morbidity were higher among survivors receiving all three treatment modalities, including chemotherapy, RT and surgery. The survey study found that a large majority of the respondents were always willing to participate future genetic studies. Study methods, study sponsorship, and health concerns affected subjects’ willingness to some degree. Ethnicity and income were independently associated with willingness to participate.Conclusion: This research identifies the late effects among YACS and the feasibility of conducting late effects studies in the future. Evidence from this work points to the importance of careful monitoring for these late health problems which could reduce the overall late effects and to the need to develop effective clinical programs and guidelines to meet the needs of this population.

View record

Master's Student Supervision (2010 - 2018)
Interactions between cytochrome P450 genetic polymorphisms and plasma organochlorines in non-Hodgkin lymphoma (2014)

Following World War II, the production of chlorine-containing organic molecules known as organochlorines (OCs) became commonplace. Although heightened regulation has since occurred in Canada, OCs continue to pose health and environmental concerns due to their persistence and ongoing use elsewhere.To date, the largest study assessing the association between plasma OCs and non-Hodgkin lymphoma (NHL) was conducted in British Columbia (BC) between 2000 and 2004. Eight hundred twenty-eight newly diagnosed NHL cases were ascertained from the BC Cancer Registry and 848 population controls were randomly obtained from the BC Ministry of Health Client Registry. Significant associations were observed between NHL and 14 individual organochlorines.Because the effects of OCs on NHL may be modified by an individual’s genetic makeup, gene-environment (GxE) interactions between OCs and cytochrome P450 (CYP) genes were examined here, using data from the subset of participants of European ethnic origin (“Europeans”) in the BC study. CYPs were chosen because they are involved in the metabolism of chemicals, including some OCs.First, the effects of the OCs were re-evaluated in Europeans only, as this was the analytic group in subsequent genetic analyses. Significant trends were noted for polychlorinated biphenyls (PCBs) 153, 180, 187, summed PCBs (total, dioxin-like, non-dioxin-like), beta-hexachlorocyclohexane (β-HCCH), hexachlorobenzene (HCB), mirex, trans-nonachlor, and oxychlordane. Significance was maintained after controlling for multiple testing for PCB-187, total summed PCBs, β-HCCH, HCB, trans-nonachlor, and oxychlordane. No significant trends were found for PCB-28, 99, 105, 118, 138, 156, 170, 183, cis-nonachlor, p, p’-DDT, or p, p’-DDE.Secondly, 129 single nucleotide polymorphisms (SNPs) in 18 CYP genes were selected for study. Significant trends were noted for rs743572 (CYP17A1) and rs1322179 (CYP2C19). Significance was not maintained after controlling for multiple testing. Two SNPs, rs9332197 and rs10509679 (CYP2C9), in the same gene cluster as CYP2C19 were of borderline non-significance.A significant GxE interaction was found between rs743572 and mirex, even after controlling for multiple testing. The increased risk of NHL conferred by higher mirex levels is lessened in minor allele homozygotes of rs743572. As CYP17A1 is involved in steroid metabolism, these results suggest the involvement of hormonal modulation in NHL risk.

View record

Mortality among British Columbians testing for hepatitis C antibody, 1992-2004 (2011)

Background: Hepatitis C virus (HCV) infection is a major preventable and treatable cause of morbidity and mortality. The ability to link records between population-based centralized laboratory HCV testing data and administrative databases has provided a unique opportunity to compare mortality and morbidity between HCV seronegative and seropositive individuals. Through the use of laboratory testing patterns and results, this study attempts to differentiate the viral effects of mortality due to HCV infection from risk behaviours/activities that are associated with acquisition of HCV infection.Methods: Serological testing data at the British Columbia (BC) Centre for Disease Control from 1992-2004 were linked to the death registry at the BC Vital Statistics Agency. Four groups of HCV testers were defined by their HCV antibody (anti-HCV) testing patterns: single non-reactive (SNR); serial multiple tested non-reactive (MNR); reactive at initial testing (REAC); and seroconverter (previously seronegative followed by reactive, a marker for incident infection) (SERO). Standardized mortality ratios were generated to compare all-cause and disease specific mortality with the BC population. Time-dependent Cox proportional hazard regression was used to compare hazard ratios among HCV serological groups.Results: Anti-HCV testers were found to have higher mortality than the BC population. Referent to the SNR group, the REAC group had higher risks for liver-related mortality (hazard ratio (HR): 9.71, 95% confidence interval (CI): 8.62-10.87) and drug-related mortality (HR: 13.51, 95% CI: 11.63-15.63). When compared to the REAC group, the SERO group had a lower risk for liver-related mortality (HR: 0.53, 95% CI: 0.24-0.92), but a higher risk for drug-related mortality (HR: 1.60, 95% CI: 1.20-2.08).Conclusions: These findings confirm that anti-HCV positive testers have increased mortality due to chronic infection related to progressive liver disease, and that a substantial proportion of the mortality is attributable to drug use and risk behaviours/activities associated with HCV acquisition. Mortality reduction in HCV infected individuals will require comprehensive prevention programming to reduce the impact of mental health and problematic substance use behaviours/activities which relate to HCV acquisition, as well as HCV treatment to prevent progression of chronic liver disease.

View record

 
 

If this is your researcher profile you can log in to the Faculty & Staff portal to update your details and provide recruitment preferences.